The majority of primate-specific regulatory sequences are derived from transposable elements.

Area of Science:

• Genomics
• Molecular Biology
• Epigenetics

Background:

• Transposable elements (TEs) are increasingly recognized for their role in genome evolution.
• Their global impact on human transcriptional networks is not fully understood.
• Emerging evidence suggests TEs contribute novel regulatory elements.

Purpose of the Study:

• To investigate the global impact of TEs on human transcriptional networks.
• To quantify the contribution of TEs to active regulatory elements in the human genome.
• To characterize the role of endogenous retroviruses (ERVs) in gene regulation.

Main Methods:

• Analysis of DNase I hypersensitivity data from ENCODE across normal, embryonic, and cancer cells.
• Identification and characterization of TE and ERV subfamily contributions to open chromatin regions.
• Investigation of TE-transcription factor interactions and sequence conservation.
• Correlation of ERV activity with cell type-specific gene expression.

Main Results:

• TEs contribute nearly half of the active regulatory elements in the human genome.
• 44% of open chromatin regions are located in TEs, rising to 63% in primate-specific regions.
• Distinct ERV subfamilies significantly contribute accessible regions, with up to 80% of instances in open chromatin.
• Thousands of ERV-derived sequences show cell type-specific activation, influencing neighboring gene expression, particularly in embryonic and cancer cells.
• TEs associated with open chromatin exhibit higher sequence conservation.

Conclusions:

• TEs, particularly ERVs, have introduced hundreds of thousands of novel regulatory elements in the primate lineage.
• TEs have substantially reshaped the human transcriptional landscape.
• ERV activity is linked to cell type-specific gene regulation, highlighting their functional importance.